Glucaffect Clinical Trial


Published on

Clinical Study done on GlucAffect. A product from Reliv International, a food science company - Mission: Nourish Our World. Better control and reversal of type 2 diabetes was noted. Best noted for blood sugar management.

  • Be the first to comment

  • Be the first to like this

No Downloads
Total views
On SlideShare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide

Glucaffect Clinical Trial

  1. 1. PHYTOTHERAPY RESEARCH Phytother. Res. (2009) Published online in Wiley InterScienceOF RELIV GLUCAFFECT™ ON BODY WEIGHT EFFECT 1 ( DOI: 10.1002/ptr.2793 Daily Consumption of Reliv Glucaffect™ for 8 Weeks Significantly Lowered Blood Glucose and Body Weight in 50 Subjects Gianni Belcaro1, Maria Cesarone1, Errichi Silvia1, Andrea Ledda1, Stefano Stuard1, Vinciguerra G1, Mark Dougall1, Umberto Cornelli1, Carl Hastings2 and Frank Schönlau3* 1 Irvine3 Vascular Labs and Physiology, Dept. of Biomedical Sciences, Gabriele D’Annunzio University, Chieti-Pescara, Italy 2 Reliv Inc., 136 Chesterfield Industrial Blvd, Chesterfield, MO 63005-1220, USA 3 Horphag Research UK Ltd, 28 Old Brompton Road, Suite 393, South Kensington, London SW7 3SS, UK A public change to healthier lifestyles with more physical activity and better nutrition, including caloric restriction, is required to address the obesity epidemic. Weight loss can be achieved by caloric restrictions; current research suggests that this may be achieved by consumption of slowly absorbed carbohydrates owing to the resulting prolonged satiety. Our rationale was to prolong the satiety of overweight volunteers by supplementation with a proprietary formulation Glucaffect™ which delays absorption of carbohydrates. Glucaffect™ provides potent α -glucosidase inhibitors of herbal source such Pycnogenol®, Madeglucyl™ and various others which obstruct absorption of carbohydrates, such as starch. Fifty overweight subjects received either Glucaffect™ or an inactive control product for eight weeks. Consumption of Glucaffect™ was found to statistically significantly lower blood-fasting glucose from baseline − 145.3 mg/dL to 101.1 mg/dL (−30.4%) and Hba1c from 7.59% to 6.33% as compared to the control group where values decreased only marginally. The weight and the body mass index (BMI) decreased significantly from an average of 88.5 kg (BMI 26.8 kg/m2) to 81.3 kg (BMI 24.5 kg/m2) as compared to the control group. In conclusion, Glucaffect™ enabled subjects with metabolic syndrome to achieve healthy BMI and blood glucose levels. Glucaffect™ was well tolerated and no subject dropped out. Copyright © 2009 John Wiley & Sons, Ltd. Keywords: BMI; metabolic syndrome; Pycnogenol™; Madeglucyl™; Weight loss. with low GI which would help control postprandial INTRODUCTION hyperglycemia. The glycemic load (GL) takes into account the GI of a food item and the amount eaten The prevalence of obesity has reached epidemic (Venn and Green, 2007). proportions worldwide and the incidence of overweight Currently, there is much interest in the potential of and obesity continues to rise. According to the World low-GI food in the management of obesity. Low-GI Health Organization (WHO) 65% of adult Americans foods may benefit weight control in two ways: by pro- are overweight with a body mass index (BMI) of moting satiety and by extending fat oxidation at the ≥25 kg/m2). expense of carbohydrate oxidation (Brand-Miller et al., Weight loss can essentially only be achieved by 2002). The theory of appetite developing in response to a change to a healthier lifestyle with more physical a transient fall in blood glucose was already introduced activity and better diet, including energy restriction. The as the ‘glucostatic theory’ in 1953 (Mayer, 1953). Regu- challenge is to achieve sustainable weight loss and lation of satiety in response to food consumption prevent weight ‘creep’ without suffering and potential appears to be significantly complicated as a multitude health risks. The modest success of low-fat diets has of peptides are released in the small intestine, which turned research toward alternative dietary strategies, interact with specific receptors of the peripheral ner- including high-protein diets and low glycemic index (GI) vous system. There is evidence from short-term studies diets (Brand-Miller et al., 2008). that low-GI foods have higher satietogenic properties The GI depicts the blood glucose response after than high-GI foods (Bornet et al., 2007). Only recently consumption of a specific carbohydrate meal relative to a clinical investigation with school children in the United a rapidly absorbed reference carbohydrate, typically Kingdom has pointed to a significantly decreased glucose or white bread. GI was originally designed for food intake when a low-GI breakfast was consumed people with diabetes as a guide for selecting food (Warren et al., 2003). A group of substances known as α -glucosidase inhibitors affect the enzyme responsible for disassemb- * Correspondence to: Frank Schonlau, Horphag Research UK Ltd, 28 Old Brompton Road, Suite 393, South Kensington, London SW7 ling complex dietary carbohydrates, such as starch, 3SS, UK. into individual glucose molecules for absorption into E-mail: the blood stream. From clinical experience with oral Copyright © 2009 John Wiley & Sons, Ltd. Received 13 November 2008 Phytother. Res. (2009) Revised 6 January 2009 DOI: 10.1002/ptr Copyright © 2009 John Wiley & Sons, Ltd. Accepted 6 January 2009
  2. 2. 2 G. BELCARO ET AL. antidiabetic medications with α-glucosidase inhibitors sugar and decreasing carbohydrate absorption were for treatment of hyperglycemia, a favorable effect for 15 mg French maritime pine bark extract Pycnogenol® decreasing body weight was found. This effect was (Horphag Research, London, UK), Syzygium cumini attributed to the non-insulinotropic mechanism of ac- extract Madeglucyl™ 500 mg (Indena, Milan, Italy), tion, and an effect on satiety (Purnell and Weyer, 2003). Salacia oblonga extract 120 mg, Pterocarpus marsupium Various herbal extracts have been described to extract Silbinol® 250 mg (Sabinsa Corporation, Piscat- inhibit α-glucosidase, such as French maritime pine away, NJ, USA), and Lagerstroemia speciosa extract bark extract Pycnogenol® (Horphag Research, London, Glucohelp™ 4 mg (Optipure, Los Angeles, CA, USA). UK) (Schäfer and Hogger, 2007), Syzygium cumini The control product did not contain any of the active Madeglucyl™ (Indena, Milan, Italy) (Teixeira et al., components but consisted exclusively of low-fat soy 2004) and Salacia oblonga (Collene et al., 2005), which flour, corn-based starch, sunflower oil, ground cinnamon all have been demonstrated to have hypoglycemic and equivalent natural and synthetic flavorings and effects in humans. In this study we describe the acesulfame sweetener to match taste, color and texture effect of a complex meal replacement formulation, of the active product. Glucaffect™ (Reliv Inc., Chesterfield, MO, USA), Subjects were advised to consume the product from containing aforementioned α-glucosidase inhibitors Monday to Saturday as a means of meal replacement plus additional natural hypoglycemic substances for with the aim to substitute up to two meals a day during controlling blood sugar and body weight in subjects 8 am and 6 pm. They were advised to have dinner and diagnosed with metabolic syndrome. were allowed to choose a meal of their choice. On Sundays they did not consume Glucaffect™ and were permitted to have food of their choice but were re- commended to have low-calorie meals with limited MATERIAL AND METHODS amounts of carbohydrates. Subjects were briefed on limiting the use of refined sugar and advised to avoid Subjects. Fifty subjects were recruited for this study sweetened beverages. after informed consent. They had a BMI ≥25 kg/m2 and A personal exercise program was suggested to sub- a fasting blood sugar above 126 mg/dL (7 mmol/L), both jects before the diet period commenced. The exercise parameters meeting the criteria for metabolic syndrome program included a total of at least 60 min exercise according to the American Diabetes Association. The each day, divided into three separate episodes per day. subjects were from central Italy (San Valentino) where Only subjects willing to adhere to the diet and exer- a typical diet often includes an excess of refined sugars cise program, with the expectation of good compliance and starch (particularly bread and pasta). and motivation, were considered for inclusion. Exclusion criteria for subjects were fasting blood Study design. Subjects were examined at enrolment glucose values exceeding 162 mg/dL (9 mmol/L) and to meet inclusion criteria and briefed on procedures any other metabolic or clinical conditions requiring one week before trial start. Patients were seen again medical treatment. Pregnant or breastfeeding females, after four weeks to monitor tolerability as well as com- individuals with any clinical condition, psychiatric pliance. On this occasion another canister of study disorders including depression, and subjects who par- material was provided to them which would last until ticipated in another study less than 30 days before the the total eight-week trial period was completed. Weekly start of this study were excluded. contacts, either personal or by phone, were maintained Subjects were randomly assigned either to the active during the study period. compound or to the control group in a single blinded Body weight and size, as well as fasting blood glu- fashion. Subjects were free to leave the trial at any cose and HbA1c levels were established using standard time. clinical equipment. Treatment. Following inclusion, subjects were sup- Statistical analysis. At least 12 subjects per group were plied with canisters containing powdered material needed to achieve statistical differences. As the dis- together with a scoop to roughly sample 12 g of pro- tribution of values was unknown, non-parametric duct for preparation of one serving. They were advised statistics were used. to prepare a serving by stirring one scoop with 12 g Results are presented as the mean ± SD. Statistical into approximately 200 ml of water and stir thoroughly. analysis of fasting blood glucose, HbA1c, weight and Four such servings were to be consumed during a day, BMI was performed with the Mann-Whitney U-test and equivalent to 48 gr Glucaffect™ powder. After four analysis of the variance. Values of p < 0.05 were con- weeks, patients were seen again to monitor tolerability sidered significant. and compliance by checking canisters. At this occasion they were supplied with another canister for the fol- lowing four weeks until trial completion. The Glucaffect™ formulation per 12-gr serving con- RESULTS sists of a base of low-fat soy flour (8.78 g), soy lecithin (150 mg), both of non-genetically modified origin, Twenty-four subjects were assigned to the active together with natural and synthetic flavoring, ground compound group receiving Glucaffect™, 14 men and cinnamon (44 mg), guar and xanthan gum (120 mg of 10 women, aged 30 to 60 years with a mean age of each), inulin (400 mg), and acesulfame potassium 42.3 years (±8.3). Twenty-six subjects were assigned to (90 mg). It is further fortified with Omega-3 fish oils the control group, 15 men and 11 women, aged 30 to (750 mg), CoQ10 (20 mg), L-Glutathione (12.5 mg) and 58 years with a mean age of 43 years (±7.1). Groups alpha lipoic acid (100 mg), respectively per serving. were comparable for age, sex, and parameters for Active components per serving for lowering blood HbA1c, fasting blood glucose and BMI. Copyright © 2009 John Wiley & Sons, Ltd. Phytother. Res. (2009) DOI: 10.1002/ptr
  3. 3. EFFECT OF RELIV GLUCAFFECT™ ON BODY WEIGHT 3 Figure 2. Development of the glycosylated hemoglobin (HbA1c) Figure 1. Development of the fasting blood glucose in the in the groups receiving either Glucaffect™ (black) or the inac- groups receiving either Glucaffect™ (black) or the inactive tive control product (gray). The subjects receiving Glucaffect™ control product (grey). The subjects receiving Glucaffect™ show show a significantly decreased HbA1c level as compared to a significantly decreased fasting blood glucose as compared to baseline (p < 0.05). The dotted line shows the 7% threshold both baseline as well as to the control group (p < 0.05). The value over which the HbA1c level is considered prediabetic ac- dotted line depicts the 126 mg/dL (7 mmol/l) threshold which cording to the American Diabetes Association. Glucaffect™ is the borderline fasting glucose above which individuals are decreases HbA1c values below the 7% mark suggesting good considered prediabetic. Glucaffect™ lowers fasting glucose in glucose control. subjects to values well below the prediabetes level. Control of returned canisters suggests good com- pliance with no more than two Glucaffect™ servings missed per week. No complications or side effects were observed during the study. No subjects dropped out. As shown in Fig. 1, consumption of four portions Glucaffect™ per day for six days a week over a total period of eight weeks lowered fasting blood glucose from a baseline average of 145.3 ± 24.5 mg/dL (8.07 ± 1.36 mmol/L) to 101.1 ± 6.2 mg/dL (5.62 ± 0.34 mmol/ L). A marginal reduction of fasting blood glucose was observed in the control group. Values decreased from baseline 143.1 ± 21 mg/dL (7.95 ± 1.17 mmol/L) to 133.0 ± 22 mg/dL (7.39 ± 1.2 mmol/L). Glucaffect™ lowered fasting blood glucose by 30.4% and this reduction was statistically significant as compared to baseline as well as to the control group. The decreased blood glucose with Glucaffect™ is reflected by a significant reduction of glycosylated Figure 3. Development of the BMI in the groups receiving either hemoglobin as shown in Fig. 2. During the eight weeks, Glucaffect™ (black) or the inactive control product (gray). HbA1c values decreased statistically significantly as Subjects receiving Glucaffect™ show a significantly decreased compared to baseline from 7.59% to 6.33%. In the BMI as compared to baseline as well as to the control group (p < 0.05). The dotted line shows BMI of 25 kg/m2, above which control group, HbA1c decreased marginally from 7.56% people are considered overweight. Consumption of Glucaffect™ to 7.3%. for eight weeks brought the BMI below a value of 25 kg/m2 It is an important finding that consumption of which represents a successful slimming effort. Glucaffect™ enabled subjects with pre-diabetic glucose levels to return to healthy blood-sugar levels. The weight and BMI of subjects taking Glucaffect™ decreased significantly as compared to baseline as well DISCUSSION as the control group (Fig. 3). At trial start, the average body weight was 88.5 ± 4.4 kg (BMI 26.8 ± 4.3 kg/m2), The development of an appetite is dependent upon which decreased to 81.3 ± 5 kg (BMI 24.5 ± 4.9 kg/m2) interactions between physiology and the environment. after eight weeks’ consumption of Glucaffect™. Thus, The environment bears extremely influential factors on average, subjects lost 7.2 kg weight within eight overriding physiologic and metabolic processes operat- weeks and on average they slimmed to an extent ing to maintain body weight in many people, not only that they achieved their optimal weight with a BMI in children. During and immediately after eating, <25 kg/m2. No significant effect on body weight was diverse physiological events are triggered which are found for the control group, in which average weight referred to as ‘satiety signals’. The satiation leads to decreased merely from 87 ± 5.0 kg (BMI 26.5 ± the termination of food intake. When satiety signals 5.0 kg/m2) to 85 ± 4.3 kg (BMI 25.99 ± 4.3 kg/m2). subside, the feeling of hunger returns, leading to the Copyright © 2009 John Wiley & Sons, Ltd. Phytother. Res. (2009) DOI: 10.1002/ptr
  4. 4. 4 G. BELCARO ET AL. consumption of the next meal. A delayed digestion and values described for acarbose in diabetic patients. This absorption of carbohydrates should stimulate nutrient cannot exclusively be attributed to α-glucosidase inhibi- receptors in the gastrointestinal tract for a longer tion, as the formulation bears further ingredients which period of time, resulting in a prolonged feedback via lower blood sugar by other modes of action (Dhanabal satiety signals. et al., 2006). Glucohelp, the extract of banana leaves Other researchers have previously demonstrated a (Lagerstroemia speciosa), contains corosolic acid which decrease of fat mass in healthy, moderately overweight was suggested to up-regulate glucose transporters for subjects using low-GI foods, by using diets rich in facilitating better glucose supply to tissues (Fukushima wholegrain (Bouché et al., 2002). There are various et al., 2006). In clinical trials, corosolic acid was described short-term studies supporting this notion as reviewed to significantly lower blood glucose. Alpha-lipoic was by Bornet et al. (2007); however, the authors conclude demonstrated in various clinical trials to have a hypo- that longer-term health benefits of ‘satietogenic food glycemic effect in humans. This effect was described to or diet’ are lacking. result from the improved insulin sensitivity with alpha- The rationale for the intervention with Glucaffect™ lipoic acid in Type 2 diabetes patients (Kamenova, was different as we attempted to slow down absorption 2006). of dietary carbohydrates of standard meals by dimin- It has been argued that unlike high-protein, low- ishing the activity of the enzyme α-glucosidase. In turn, carbohydrate (Atkins-style) or very high carbohydrate the decreased degradation of complex carbohydrates, diets with their potential for adverse effects, there would predominantly starch, leads to a much slower absorp- be no safety concerns surrounding low-GI diets (Brand- tion, decreased insulin secretion and prolonged satiety Miller et al., 2008). As shown for low-GI diets, the (Heacock et al., 2005). A typical substance with this consumption of Glucaffect™ improved glycosylated pharmacologic profile is acarbose, widely used for treat- hemoglobin levels without increasing LDL-cholesterol ing hyperglycemia (Laube, 2002). In clinical trials on or the risk of hypoglycemia. treatment of hyperglycemia it was noticed that acarbose A major factor in our study was that subjects managed has a favorable effect on body weight (Purnell and to skip two meals a day over weeks with the exception Weyer, 2003). Acarbose has been successfully tested of Sundays. The latter was a concession to Italian for controlling body weight in hyperinsulinaemic women lifestyle, which, on the other hand, ensured that subjects with polycystic ovarian syndrome, which showed a otherwise strictly followed the protocol. The massively significant reduction of BMI after six months of treat- decreased caloric intake surely did not only further ment (Penna et al., 2005). contribute to the lowering of blood glucose but explains Substances like French maritime pine bark extract the surprising loss of weight of subjects. The average Pycnogenol® have recently been shown to exceed the lowering of BMI by more than 2 kg/m2 and 7.2 kg potency for inhibition of α-glucosidase of acarbose body weight within two months was more than we by two orders of magnitude (Schäfer and Hogger, anticipated. 2007). In a clinical trial, a daily total dosage of 50 mg Pycnogenol® affected carbohydrate absorption for sig- nificantly decreasing postprandial blood glucose after three weeks by 10.5% (Liu et al., 2004). There are CONCLUSION several herbal extracts which have been described to inhibit the activity of α-glucosidase, and these, together This study provides evidence that consumption of with Pycnogenol®, have therefore been chosen for crea- Glucaffect™ has a positive effect for keeping blood tion of the Glucaffect™ formulation. Salacia oblonga sugar in a healthy range and allows for reducing caloric extract was recently demonstrated to lower post- intake with a resulting loss of weight when applied in prandial glucose peaks after a carbohydrate-rich meal conjunction with a healthier lifestyle involving better because of α-glucosidase inhibition (Williams et al., nutrition and regular moderate exercise. 2007). Inulin was further added because this indiges- tible sweet-tasting polysaccharide supports the percep- tion of satiety. Acknowledgements For our study we chose prediabetic, overweight subjects for whom we suspected a particularly high The authors wish to thank Mr David Huesgen of Reliv Inc., for his invaluable help and tireless coordination on information exchange impact for lowering blood glucose. The decrease of and investigational material logistics between the US manufacturers fasting blood glucose as well as HbA1c in our subjects and researchers in Europe. The study was sponsored by a research after two months’ consumption of Glucaffect™ exceeds grant from Horphag Research UK Ltd. REFERENCES Bornet FR, Jardy-Gennetier AE, Jacquet N, Stowell J. 2007. Brand-Miller J, McMillan-Price J, Steinbeck K, Caterson I. 2008. Glycaemic response to foods: impact on satiety and long- Carbohydrates – the good, the bad and the whole grain. term weight regulation. Appetite 49: 535–553. Asia Pac J Clin Nutr 17(Suppl 1): 16–19. Bouché C, Rizkalla SW, Luo J, Vidal H, Veronese A, Pacher N, Collene AL, Hertzler SR, Williams JA, Wolf BW. 2005. Effects of Fouquet C, Lang V, Slama G. 2002. Five-week, low-glycemic a nutritional supplement containing Salacia oblonga extract index diet decreases total fat mass and improves plasma and insulinogenic amino acids on postprandial glycemia, lipid profile in moderately overweight nondiabetic men. insulinemia, and breath hydrogen responses in healthy Diabetes Care 25: 822–828. adults. Nutrition 21: 848–854. Brand-Miller JC, Holt SH, Pawlak DB, McMillan J. 2002. Dhanabal SP, Kokate CK, Ramanathan M, Kumar EP, Suresh B. Glycemic index and obesity. Am J Clin Nutr 76: 281S– 2006. Hypoglycaemic activity of Pterocarpus marsupium 285S. Roxb. Phytother Res 20: 4–8. Copyright © 2009 John Wiley & Sons, Ltd. Phytother. Res. (2009) DOI: 10.1002/ptr
  5. 5. EFFECT OF RELIV GLUCAFFECT™ ON BODY WEIGHT 5 Fukushima M, Matsuyama F, Ueda N, Egawa K, Takemoto J, Purnell JQ, Weyer C. 2003. Weight effect of current and Kajimoto Y, Yonaha N, Miura T, Kaneko T, Nishi Y, Mitsui experimental drugs for diabetes mellitus: from promotion R, Fujita Y, Yamada Y, Seino Y. 2006. Effect of corosolic to alleviation of obesity. Treat Endocrinol 2: 33–47. acid on postchallenge plasma glucose levels. Diabetes Res Schäfer A, Högger P. 2007. Oligomeric procyanidins of French Clin Pract 73: 174–177. maritime pine bark extract (Pycnogenol®) effectively inhibit Heacock PM, Hertzler SR, Williams JA, Wolf BW. 2005. Effects alpha-glucosidase. Diabetes Res Clin Pract 77: 41–46. of a medical food containing an herbal alpha-glucosidase Teixeira CC, Weinert LS, Barbosa DC, Ricken C, Esteves JF, inhibitor on postprandial glycemia and insulinemia in Fuchs FD. 2004. Syzygium cumini (L.) Skeels in the treatment healthy adults. J Am Diet Assoc 105: 65–71. of type 2 diabetes: results of a randomized, double-blind, Kamenova P. 2006. Improvement of insulin sensitivity in patients double-dummy, controlled trial. Diabetes Care 27: 3019– with type 2 diabetes mellitus after oral administration of 3020. alpha-lipoic acid. Hormones (Athens) 5: 251–258. Venn BJ, Green TJ. 2007. Glycemic index and glycemic load: Laube H. 2002. Acarbose. Clin Drug Invest 22: 141–156. measurement issues and their effect on diet-disease rela- Liu X, Zhou HJ, Rohdewald P. 2004. French maritime pine bark tionships. Eur J Clin Nutr 61 Suppl 1: 122–131. extract Pycnogenol® dose-dependently lowers glucose in Warren JM, Henry CJ, Simonite V. 2003. Low glycemic index type II diabetes patients. Diabetes Care 27: 839. breakfasts and reduced food intake in preadolescent Mayer J. 1953. Glucostatic mechanism of the regulation of food children. Pediatrics 112: 414–419. intake. New England J Med 249: 13–16. Williams JA, Choe YS, Noss MJ, Baumgartner CJ, Mustad VA. Penna IA, Canella PR, Reis RM, Silva de Sá MF, Ferriani RA. 2007. Extract of Salacia oblonga lowers acute glycemia 2005. Acarbose in obese patients with polycystic ovarian in patients with type 2 diabetes. Am J Clin Nutr 86: syndrome: a double-blind, randomized, placebo-controlled 124–130. study. Hum Reprod 20: 2396–2401. Copyright © 2009 John Wiley & Sons, Ltd. Phytother. Res. (2009) DOI: 10.1002/ptr